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BioAssay: AID 552558

Inhibition of human WNK2 at 10 uM after 60 mins by TR-FRET assay

In this Letter, we describe the discovery of selective JNK2 and JNK3 inhibitors, such as 10, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs, p38I+/- and ERK2. Substitution of the naphthalene ring affords an isoform selective JNK3 inhibitor, 30, with approximately 10-fold selectivity over both JNK1 and JNK2. A naphthalene ring penetrates deep into the selectivity pocket accounting for the differentiation amongst the kinases. Interestingly, the gatekeeper Met146 sulfide interacts with the naphthalene ring in a sulfur-I ..more
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 Tested Compounds
 Tested Compounds
All(1)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(1)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 552558
Data Source: ChEMBL (701086)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2011-09-18
Modify Date: 2014-05-26

Data Table ( Complete ):           All
Target
Sequence: RecName: Full=Serine/threonine-protein kinase WNK2; AltName: Full=Antigen NY-CO-43; AltName: Full=Protein kinase lysine-deficient 2; AltName: Full=Protein kinase with no lysine 2; AltName: Full=Serologically defined colon cancer antigen 43
Description ..   
Protein Family: Catalytic domain of Protein Kinases
Comment ..   

Gene:WNK2     Related Protein 3D Structures     More BioActivity Data..
Tested Compound:
Description:
Title: Highly selective c-Jun N-terminal kinase (JNK) 2 and 3 inhibitors with in vitro CNS-like pharmacokinetic properties prevent neurodegeneration.

Abstract: In this Letter, we describe the discovery of selective JNK2 and JNK3 inhibitors, such as 10, that routinely exhibit >10-fold selectivity over JNK1 and >1000-fold selectivity over related MAPKs, p38I+/- and ERK2. Substitution of the naphthalene ring affords an isoform selective JNK3 inhibitor, 30, with approximately 10-fold selectivity over both JNK1 and JNK2. A naphthalene ring penetrates deep into the selectivity pocket accounting for the differentiation amongst the kinases. Interestingly, the gatekeeper Met146 sulfide interacts with the naphthalene ring in a sulfur-I
(PMID: 21112785)
Categorized Comment
Assay Type: Binding

Assay Data Source: Scientific Literature

BAO: Assay Format: biochemical format

Target Type: Target is a single protein chain

Result Definitions
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Inhibition activity commentInhibition activity commentString
2Inhibition standard flagInhibition standard flagInteger
3Inhibition qualifierInhibition qualifierString
4Inhibition published valueInhibition published valueFloat%
5Inhibition standard valueInhibition standard valueFloat%

Data Table (Concise)
Classification
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